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EC number: 203-157-5 | CAS number: 103-90-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other:
Data source
Reference
- Reference Type:
- publication
- Title:
- Effects of Acetaminophen on Preimplantation Embryo Glutathione Concentration and Development in Vivo and in Vitro
- Author:
- Delia N. Laub, Nawal O. Elmagbari, Nura M Elmagbari, Melissa A. Hausburg, and Catherine S. Gardinerl
- Year:
- 2 000
- Bibliographic source:
- TOXICOICAL SCIENCES 56, 150-155 (2000)
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- Effects of Acetaminophen on Preimplantation Embryo
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Paracetamol
- EC Number:
- 203-157-5
- EC Name:
- Paracetamol
- Cas Number:
- 103-90-2
- Molecular formula:
- C8H9NO2
- IUPAC Name:
- .
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- not specified
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:Harlan (Indianapolis, IN).
- Age at study initiation: (P) x wks; (F1) x wks
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g
- Use of restrainers for preventing ingestion (if dermal): yes/no
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
IN-LIFE DATES: From: To: No data
Administration / exposure
- Route of administration:
- other: Intragastrically
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: 0.5% tragacanth solution
- Details on exposure:
- APAP was given daily from 8 days prior to ovulation until day 3 of gestation.
- Details on mating procedure:
- Females were bred with proven breeder males and were checked the next day for a copulation plug (designated as day 0 of gestation).
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 8 days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0 or 1430 mg/kg of body weight
Basis:
- No. of animals per sex per dose:
- Control:
36 females
1430 mg/kg:
36 females - Control animals:
- yes, concurrent vehicle
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: No data
- Time schedule:
- Cage side observations checked in table were included.
BODY WEIGHT: Yes
- Upon evaluation of the females on d17 of gestation, maternal body weight did not differ significantly.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: - Statistics:
- Morphological development was analyzed using Kruskal-Wallis analysis of variance. Analysis of variance and least-significant- difference procedures were used to determine differences in GSH and GSSG content of embryos, liver, and ovaries. A t-test was used to analyze the number of fetuses per dam, number of resorptions per dam,individual fetal weight, total fetal weight, uterine weight, liver weight, and weight of dam on d17. Chi-square analysis was used to analyze the number of mice with copulation plugs and the number of deceased mice. Statistica software was used for statistical analysis. All experiments were repeated at least twice with a `minimum of 3 replications for each treatment each time.
- Offspring viability indices:
- Liver and ovary collection and evaluation: Portions of the liver and both ovaries were dissected from euthanized female mice and weighed. The overall morphology of the tissues was assessed, and the samples were prepared for quantification of GSH.
Fetus coHection and evaluation. :Female pubertal mice were bred with proven breeder males on day -1. On d17 of gestation, dams were euthanized and fetuses were removed via cesarean section. Maternal and fetal evaluation consisted of recording the number of resorptions in the uterus, weighing the intact uterus with the fetuses, weighing the pregnant dam, examining each fetus for gross malformations, weighing individual fetuses, and noting the number of pups per liner
ElTects of one dose of APAP on GSH concentration and embryo develop- ment in vivo:. Mice found to have copulation plugs on do were treated on d2 with 0, 800, or 1430 mg APAP/kg. Mice were euthanized, and samples were collected 12 h after dosing.
Enects of preimplantation exposure with APAP on development to term. :Female mice were treated with 0 or 1430 mg|kg APAP daily starting 8 days prior to ovulation and continuing until 3 days after copulation plugs were detected. Fetuses were removed by cesarean section on d17 of gestation
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 9 mice treated with APAP died during the course of the study.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 9 mice treated with APAP died during the course of the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Upon evaluation of the females on d17 of gestation, maternal body weight did not differ significantly .
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Description (incidence and severity):
- significantly fewer female mice were found with copulation plugs each day of breeding in the 1430 mg/kg APAP group .
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- Administration of one dose of APAP intragastrically to pregnant female mice on d2 of gestation significantly decreased liver GSH concentrations.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 430 other: mg/kg
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Copulation plugs each day of breeding, decreased liver GSH concentrations
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- chnges in number of live fetuses was observed.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- changes were observed at higher dose.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- changes in uterine weights.
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 430 other: mg/kg
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: live fetuses, body weights,uterine weights
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The NOAEL (no observed adversed effect level ) of Acetaminophen in female mice and offsprings were observed at a dose level of 1430 mg/kg.
- Executive summary:
Effects of Acetaminophen on Preimplantation Embryos were studied in pregnant mice. APAP (Acetaminophen) was given daily at a dosge of 0 or 1430 mg/kg from 8 days prior to ovulation until day 3 of gestation.Different parameters like GSH concentration and embryo development in vivo, body weight,organ weight, resorptions and live fetuses were analyzed.Upon evaluation of the females on d 17 of gestation, maternal body weight did not differ significantly, nor did liver or uterine weight, and significantly fewer female mice were found with copulation plugs each day of breeding in the 1430 mg/kg APAP group. While no mice died in the control group, 9 mice treated with APAP died during the course of the study. No gross malformations were found, but individual fetuses from females treated with APAP weighed significantly more than fetuses from the control dams. Thus we can conclude that the NOAELs (no observed adverse effect levels) of Acetaminophen in female mice and offspring were observed atadose level of 1430 mg/kg.
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